DESCRIPTION OF OVERALL CENTER (provided by applicant): The Harvard Digestive Diseases Center (HDDC) is a consortium of 60 independent investigators. 22 Associate Members approaching independence and over 200 trainees also participate in HDDC activities. The scientific focus of the Center is the epithelium of the gastrointestinal tract and its interactions with the microbial flora in the lumen, and with immunocompetent and supporting cell types in the mucosa. Our title "Integrated Epithelial and Mucosal Biology" describes this focus. Our goal is to facilitate multidisciplinary research in the field by fostering close scientific and intellectual relationships among independent investigators in Harvard-affiliated hospitals, the Harvard Medical School and adjacent research institutions in the Longwood Medical Area. Drs. Wayne Lencer (PI) and Richard Blumberg (Co-PI) will direct the Center. They are scientific colleagues and Division Chiefs of Pediatric and Adult Gl at two major Harvard teaching hospitals. Both direct NIH funded training programs. The Directors and Executive Committee provide leadership with tremendous scientific depth and commitment to digestive diseases related research. Three scientific cores enhance this effort by providing services, materials, equipment, and expertise. The Imaging Core B provides resources in immunofluorecence, electron microscopy, confocal, and deconvolution microscopy of living and fixed cells and tissues. The Epithelial Cell Biology Core C provides cell culture and gene transaction services unique to polarized epithelial cell monolayers, and assistance in all aspects of epithelial cell biology including electrophysiology, microflorimetry, and molecular approaches to signal transduction and membrane dynamics. A new Proteomics Core D provides service in protein identification, quantitation and characterization by 2D PAGE, affinity tags, and mass spectrometry. The HDDC enrichment program includes an annual regional conference "Frontiers in Mucosal Immunology", as well as two scientific symposia each year. The minisabbatical program supports travel of HDDC members to other institutions to learn new techniques. The HDDC pilot-feasibility grant program is highly subscribed and funded to the maximum level allowed;of 49 awardees in the past 10 years, almost all continue in digestive diseases related research. An innovative seed grant program is planned to foster new collaborative projects among established HDDC investigators, and a biostatistics resource is planned to support translational and basic science. Through the intellectual richness of the membership base, scientific cores, grant programs and enrichment opportunities, the HDDC continues to support the training of junior investigators and to attract established investigators from other fields, advancing broad areas of research relevant to digestive diseases.